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917300.9982Bacterial defences: mechanisms, evolution and antimicrobial resistance. Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.202337095190
826710.9980Why put up with immunity when there is resistance: an excursion into the population and evolutionary dynamics of restriction-modification and CRISPR-Cas. Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction-modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions under which selection mediated by lytic phage will favour such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.201930905282
827820.9980Siderophore cheating and cheating resistance shape competition for iron in soil and freshwater Pseudomonas communities. All social organisms experience dilemmas between cooperators performing group-beneficial actions and cheats selfishly exploiting these actions. Although bacteria have become model organisms to study social dilemmas in laboratory systems, we know little about their relevance in natural communities. Here, we show that social interactions mediated by a single shareable compound necessary for growth (the iron-scavenging pyoverdine) have important consequences for competitive dynamics in soil and pond communities of Pseudomonas bacteria. We find that pyoverdine non- and low-producers co-occur in many natural communities. While non-producers have genes coding for multiple pyoverdine receptors and are able to exploit compatible heterologous pyoverdines from other community members, producers differ in the pyoverdine types they secrete, offering protection against exploitation from non-producers with incompatible receptors. Our findings indicate that there is both selection for cheating and cheating resistance, which could drive antagonistic co-evolution and diversification in natural bacterial communities.Lab strains of Pseudomonas are model systems for the evolution of cooperation over public goods (iron-scavenging siderophores). Here, Butaitė et al. add ecological and evolutionary insight into this system by showing that cheating and resistance to cheating both shape competition for iron in natural Pseudomonas communities.201728871205
958330.9980Bacteriophages presence in nature and their role in the natural selection of bacterial populations. Phages are the obligate parasite of bacteria and have complex interactions with their hosts. Phages can live in, modify, and shape bacterial communities by bringing about changes in their abundance, diversity, physiology, and virulence. In addition, phages mediate lateral gene transfer, modify host metabolism and reallocate bacterially-derived biochemical compounds through cell lysis, thus playing an important role in ecosystem. Phages coexist and coevolve with bacteria and have developed several antidefense mechanisms in response to bacterial defense strategies against them. Phages owe their existence to their bacterial hosts, therefore they bring about alterations in their host genomes by transferring resistance genes and genes encoding toxins in order to improve the fitness of the hosts. Application of phages in biotechnology, environment, agriculture and medicines demands a deep insight into the myriad of phage-bacteria interactions. However, to understand their complex interactions, we need to know how unique phages are to their bacterial hosts and how they exert a selective pressure on the microbial communities in nature. Consequently, the present review focuses on phage biology with respect to natural selection of bacterial populations.202033170167
958940.9979Phage Therapy: Going Temperate? Strictly lytic phages have been consensually preferred for phage therapy purposes. In contrast, temperate phages have been avoided due to an inherent capacity to mediate transfer of genes between bacteria by specialized transduction - an event that may increase bacterial virulence, for example, by promoting antibiotic resistance. Now, advances in sequencing technologies and synthetic biology are providing new opportunities to explore the use of temperate phages for therapy against bacterial infections. By doing so we can considerably expand our armamentarium against the escalating threat of antibiotic-resistant bacteria.201930466900
917250.9979These Are the Genes You're Looking For: Finding Host Resistance Genes. Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host-bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.202133004258
958160.9979Lateral gene transfer, bacterial genome evolution, and the Anthropocene. Lateral gene transfer (LGT) has significantly influenced bacterial evolution since the origins of life. It helped bacteria generate flexible, mosaic genomes and enables individual cells to rapidly acquire adaptive phenotypes. In turn, this allowed bacteria to mount strong defenses against human attempts to control their growth. The widespread dissemination of genes conferring resistance to antimicrobial agents has precipitated a crisis for modern medicine. Our actions can promote increased rates of LGT and also provide selective forces to fix such events in bacterial populations. For instance, the use of selective agents induces the bacterial SOS response, which stimulates LGT. We create hotspots for lateral transfer, such as wastewater systems, hospitals, and animal production facilities. Conduits of gene transfer between humans and animals ensure rapid dissemination of recent transfer events, as does modern transport and globalization. As resistance to antibacterial compounds becomes universal, there is likely to be increasing selection pressure for phenotypes with adverse consequences for human welfare, such as enhanced virulence, pathogenicity, and transmission. Improved understanding of the ecology of LGT could help us devise strategies to control this fundamental evolutionary process.201727706829
826670.9978Remarkable Mechanisms in Microbes to Resist Phage Infections. Bacteriophages (phages) specifically infect bacteria and are the most abundant biological entities on Earth. The constant exposure to phage infection imposes a strong selective pressure on bacteria to develop viral resistance strategies that promote prokaryotic survival. Thus, this parasite-host relationship results in an evolutionary arms race of adaptation and counteradaptation between the interacting partners. The evolutionary outcome is a spectrum of remarkable strategies used by the bacteria and phages as they attempt to coexist. These approaches include adsorption inhibition, injection blocking, abortive infection, toxin-antitoxin, and CRISPR-Cas systems. In this review, we highlight the diverse and complementary antiphage systems in bacteria, as well as the evasion mechanisms used by phages to escape these resistance strategies.201426958724
959580.9978Targeted antibiotic discovery through biosynthesis-associated resistance determinants: target directed genome mining. Intense competition between microbes in the environment has directed the evolution of antibiotic production in bacteria. Humans have harnessed these natural molecules for medicinal purposes, magnifying them from environmental concentrations to industrial scale. This increased exposure to antibiotics has amplified antibiotic resistance across bacteria, spurring a global antimicrobial crisis and a search for antibiotics with new modes of action. Genetic insights into these antibiotic-producing microbes reveal that they have evolved several resistance strategies to avoid self-toxicity, including product modification, substrate transport and binding, and target duplication or modification. Of these mechanisms, target duplication or modification will be highlighted in this review, as it uniquely links an antibiotic to its mode of action. We will further discuss and propose a strategy to mine microbial genomes for these genes and their associated biosynthetic gene clusters to discover novel antibiotics using target directed genome mining.201930985219
836290.9978Lifestyle evolution in symbiotic bacteria: insights from genomics. Bacteria that live only in eukaryotic cells and tissues, including chronic pathogens and mutualistic bacteriocyte associates, often possess a distinctive set of genomic traits, including reduced genome size, biased nucleotide base composition and fast polypeptide evolution. These phylogenetically diverse bacteria have lost certain functional categories of genes, including DNA repair genes, which affect mutational patterns. However, pathogens and mutualistic symbionts retain loci that underlie their unique interaction types, such as genes enabling nutrient provisioning by mutualistic bacteria-inhabiting animals. Recent genomic studies suggest that many of these bacteria are irreversibly specialized, precluding shifts between pathogenesis and mutualism.200010884696
9477100.9978The microbiome-shaping roles of bacteriocins. The microbiomes on human body surfaces affect health in multiple ways. They include not only commensal or mutualistic bacteria but also potentially pathogenic bacteria, which can enter sterile tissues to cause invasive infection. Many commensal bacteria produce small antibacterial molecules termed bacteriocins that have the capacity to eliminate specific colonizing pathogens; as such, bacteriocins have attracted increased attention as potential microbiome-editing tools. Metagenome-based and activity-based screening approaches have strongly expanded our knowledge of the abundance and diversity of bacteriocin biosynthetic gene clusters and the properties of a continuously growing list of bacteriocin classes. The dynamic acquisition, diversification or loss of bacteriocin genes can shape the fitness of a bacterial strain that is in competition with bacteriocin-susceptible bacteria. However, a bacteriocin can only provide a competitive advantage if its fitness benefit exceeds the metabolic cost of production, if it spares crucial mutualistic partner strains and if major competitors cannot develop resistance. In contrast to most currently available antibiotics, many bacteriocins have only narrow activity ranges and could be attractive agents for precision therapy and prevention of infections. A common scientific strategy involving multiple disciplines is needed to uncover the immense potential of microbiome-shaping bacteriocins.202134075213
8334110.9978Tumour progression: random mutations or an integrated survival response to cellular stress conserved from unicellular organisms? The current paradigm states that cancer progression is caused by random independent mutations, each selected for its survival advantages. The accelerated rates of phenotypic changes, the pleiotropic effect of several genes involved in progression--which need not be necessarily mutated for inducing the observed changes in cancer cell behaviour--lead us to propose an alternative hypothesis. Malignant progression might be a result of the unveiling of a cell-survival program, induced by various aggressions in the same way as the SOS system is induced and regulated in bacteria. This hypothesis depends on the homology between several genes involved in cancer progression (such as bcl2, mdm2, the mismatch repair genes, the heat shock protein genes, the pleiotropic resistance genes, the telomerase gene ...) and several genes involved in the survival of prokaryotes and eukaryotes under stress. The development of multicellular organisms could not take place without the building of a control program, exemplified by the so-called anti-oncogenes. However, this control program had to integrate some weaknesses, in order to allow for embryogenesis, growth, and wound healing. These weaknesses, neutral from an evolutionary point of view--since most cancers are sporadic and kill their hosts long after the birth of the offspring--are exploited by the survival program of individual cells, inherited from the genome of prokaryotes and unicellular eukaryotes, and repressed but not suppressed in animals. If this theory is true, it is probable that (i) no anti-oncogenes will be found in unicellular organisms, (ii) the sensitivity to mutations will be higher in genes involved in proliferation and in anti-oncogenes such as p53 and Rb, than in genes not involved in the cancer process, (iii) a process of transfer of genetic information exists in cancer cells as it exists in bacteria. The identification of the genes governing the survival program could lead to new therapeutic approaches.19968733476
9580120.9977Antibiotic resistance in bacterial communities. Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic resistance, in particular, is not just a property of individual bacteria or even single-strain populations, but depends heavily on the community context. Collective community dynamics can lead to counterintuitive eco-evolutionary effects like survival of less resistant bacterial populations, slowing of resistance evolution, or population collapse, yet these surprising behaviors are often captured by simple mathematical models. In this review, we highlight recent progress - in many cases, advances driven by elegant combinations of quantitative experiments and theoretical models - in understanding how interactions between bacteria and with the environment affect antibiotic resistance, from single-species populations to multispecies communities embedded in an ecosystem.202337054512
8327130.9977'Big things in small packages: the genetics of filamentous phage and effects on fitness of their host'. This review synthesizes recent and past observations on filamentous phages and describes how these phages contribute to host phentoypes. For example, the CTXφ phage of Vibrio cholerae encodes the cholera toxin genes, responsible for causing the epidemic disease, cholera. The CTXφ phage can transduce non-toxigenic strains, converting them into toxigenic strains, contributing to the emergence of new pathogenic strains. Other effects of filamentous phage include horizontal gene transfer, biofilm development, motility, metal resistance and the formation of host morphotypic variants, important for the biofilm stress resistance. These phages infect a wide range of Gram-negative bacteria, including deep-sea, pressure-adapted bacteria. Many filamentous phages integrate into the host genome as prophage. In some cases, filamentous phages encode their own integrase genes to facilitate this process, while others rely on host-encoded genes. These differences are mediated by different sets of 'core' and 'accessory' genes, with the latter group accounting for some of the mechanisms that alter the host behaviours in unique ways. It is increasingly clear that despite their relatively small genomes, these phages exert signficant influence on their hosts and ultimately alter the fitness and other behaviours of their hosts.201525670735
9582140.9977Humans and Microbes: A Systems Theory Perspective on Coevolution. The issue of rapid adaptation of microorganisms to changing environments is examined. The mechanism of adaptive mutations is analyzed. The possibility that horizontal gene transfer is a random process is discussed. Bacteria, unicellular fungi, and other microorganisms successfully adapt to fast-changing conditions (such as exposure to drugs) because their evolution is not a random process. Adaptation to antibiotics, adaptive mutations, and related phenomena occur because microbial evolution is inherently directed and purposefully oriented toward potential external changes. Rejecting gene-centricity plays a crucial role in understanding the coevolution of humans and pathogens. This means that beyond genes, there exists a higher-level system-an organism with its own unique properties that cannot be reduced to genes. The problem of human adaptation to infectious agents (viruses, bacteria, and protozoa) is also analyzed. Based on general systems theory, it is concluded that humans and pathogens coevolve in a controlled manner.202541176022
9376150.9977Historical Contingency Drives Compensatory Evolution and Rare Reversal of Phage Resistance. Bacteria and lytic viruses (phages) engage in highly dynamic coevolutionary interactions over time, yet we have little idea of how transient selection by phages might shape the future evolutionary trajectories of their host populations. To explore this question, we generated genetically diverse phage-resistant mutants of the bacterium Pseudomonas syringae. We subjected the panel of mutants to prolonged experimental evolution in the absence of phages. Some populations re-evolved phage sensitivity, whereas others acquired compensatory mutations that reduced the costs of resistance without altering resistance levels. To ask whether these outcomes were driven by the initial genetic mechanisms of resistance, we next evolved independent replicates of each individual mutant in the absence of phages. We found a strong signature of historical contingency: some mutations were highly reversible across replicate populations, whereas others were highly entrenched. Through whole-genome sequencing of bacteria over time, we also found that populations with the same resistance gene acquired more parallel sets of mutations than populations with different resistance genes, suggesting that compensatory adaptation is also contingent on how resistance initially evolved. Our study identifies an evolutionary ratchet in bacteria-phage coevolution and may explain previous observations that resistance persists over time in some bacterial populations but is lost in others. We add to a growing body of work describing the key role of phages in the ecological and evolutionary dynamics of their host communities. Beyond this specific trait, our study provides a new insight into the genetic architecture of historical contingency, a crucial component of interpreting and predicting evolution.202235994371
8328160.9977The Diverse Impacts of Phage Morons on Bacterial Fitness and Virulence. The viruses that infect bacteria, known as phages, are the most abundant biological entity on earth. They play critical roles in controlling bacterial populations through phage-mediated killing, as well as through formation of bacterial lysogens. In this form, the survival of the phage depends on the survival of the bacterial host in which it resides. Thus, it is advantageous for phages to encode genes that contribute to bacterial fitness and expand the environmental niche. In many cases, these fitness factors also make the bacteria better able to survive in human infections and are thereby considered pathogenesis or virulence factors. The genes that encode these fitness factors, known as "morons," have been shown to increase bacterial fitness through a wide range of mechanisms and play important roles in bacterial diseases. This review outlines the benefits provided by phage morons in various aspects of bacterial life, including phage and antibiotic resistance, motility, adhesion and quorum sensing.201930635074
9185170.9977The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications? Extended overuse and misuse of antibiotics and other antibacterial agents has resulted in an antimicrobial resistance crisis. Bacteriophages, viruses that infect bacteria, have emerged as a legitimate alternative antibacterial agent with a wide scope of applications which continue to be discovered and refined. However, the potential of some bacteriophages to aid in the acquisition, maintenance, and dissemination of negatively associated bacterial genes, including resistance and virulence genes, through transduction is of concern and requires deeper understanding in order to be properly addressed. In particular, their ability to interact with mobile genetic elements such as plasmids, genomic islands, and integrative conjugative elements (ICEs) enables bacteriophages to contribute greatly to bacterial evolution. Nonetheless, bacteriophages have the potential to be used as therapeutic and biocontrol agents within medical, agricultural, and food processing settings, against bacteria in both planktonic and biofilm environments. Additionally, bacteriophages have been deployed in developing rapid, sensitive, and specific biosensors for various bacterial targets. Intriguingly, their bioengineering capabilities show great promise in improving their adaptability and effectiveness as biocontrol and detection tools. This review aims to provide a balanced perspective on bacteriophages by outlining advantages, challenges, and future steps needed in order to boost their therapeutic and biocontrol potential, while also providing insight on their potential role in contributing to bacterial evolution and survival.202133670836
8264180.9977Anti-CRISPR Phages Cooperate to Overcome CRISPR-Cas Immunity. Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts phage replication and epidemiology. Here, we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage blocking the host CRISPR-Cas immune system to allow a second Acr-phage to successfully replicate. This cooperation leads to epidemiological tipping points in which the initial density of Acr-phage tips the balance from phage extinction to a phage epidemic. Furthermore, both higher levels of CRISPR-Cas immunity and weaker Acr activities shift the tipping points toward higher initial phage densities. Collectively, these data help elucidate how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics.201830033365
8636190.9977Insights into the synthesis, engineering, and functions of microbial pigments in Deinococcus bacteria. The ability of Deinococcus bacteria to survive in harsh environments, such as high radiation, extreme temperature, and dryness, is mainly attributed to the generation of unique pigments, especially carotenoids. Although the limited number of natural pigments produced by these bacteria restricts their industrial potential, metabolic engineering and synthetic biology can significantly increase pigment yield and expand their application prospects. In this study, we review the properties, biosynthetic pathways, and functions of key enzymes and genes related to these pigments and explore strategies for improving pigment production through gene editing and optimization of culture conditions. Additionally, studies have highlighted the unique role of these pigments in antioxidant activity and radiation resistance, particularly emphasizing the critical functions of deinoxanthin in D. radiodurans. In the future, Deinococcus bacterial pigments will have broad application prospects in the food industry, drug production, and space exploration, where they can serve as radiation indicators and natural antioxidants to protect astronauts' health during long-term space flights.202439119139